Breast cancer is a common disease, with one in eight women affected by the age of 85. It strikes more than 200,000 women each year; and 44,000 of these women will die of their disease1. There is a compelling need to diagnose and treat breast cancer more effectively. Moreover, earlier disease stage at diagnosis correlates directly with improved survival1. Local and systemic treatments cure a substantial proportion of early-stage patients2,3. Hence, improvements in screening and early detection will unequivocally save lives.
Breast cancer is a heterogeneous disease, with several phenotypic distinctions and with an unpredictable clinical course4-6. Molecular markers are used to define subsets of tumors. Useful classification is achieved by determination of the estrogen receptor, progesterone receptor, and HER2 content of cancer cells7,8. Recently, finer classification was performed using genome-wide RNA expression arrays9. In general, HER2-positive tumors segregate in a unique subset of human breast cancers, substantiating the importance of this oncogenic protein. A clinically useful classification divides breast cancer into hormone receptor positive tumors, HER2 positive tumors and tumors negative for both markers. These clinical distinctions are important for treatment response, and it is likely they effect identification of sensitive and specific diagnostic biomarkers as well.
Currently screening mammography is the mainstay for breast cancer detection. However, at least 10% of breast cancers cannot be visualized with mammography because they do not create a change in the density or architecture of breast tissue10. Only marginal benefits are demonstrated in woman under age 50 subjected to annual screening mammography10. To complement screening with mammography, there are few serum markers of any clinical utility in breast cancer and none that are useful for early detection. Markers used in clinical practice (such as CEA, CA 15.3) reflect tumor burden and are useful for addressing questions of response to therapy rather than diagnosis11. Other markers have been evaluated,12,13 but lack the sensitivity and specificity to serve as diagnostic biomarkers for breast cancer. There is a need for a broader-based approach to biomarker discovery and tests that will complement mammography.